Phase I/II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Recurrent High Grade Glioma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant glioma, including any of the following subtypes:

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Glioblastoma multiforme

- Progressive or recurrent disease after radiation therapy with or without chemotherapy

- Patients with a previous low-grade glioma that has progressed to
biopsy-confirmed high-grade glioma after radiation therapy with or without
chemotherapy are eligible

- Contrast-enhancing measurable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Absolute neutrophil count ≥ 1,500/mm³

- Hemoglobin ≥ 9 g/dL

- Platelet count ≥ 100,000/mm³

- Creatinine ≤ 1.5 mg/dL

- Bilirubin ≤ 1.5 mg/dL

- Transaminases ≤ 4 times upper limit of normal

- PT/PTT/INR normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 2 months
after completion of study treatment

- Mini Mental State Exam score ≥ 15

- No serious concurrent infection or medical illness that would impair the ability to
safely receive study treatment

- No other prior or concurrent malignancy within the past 5 years except for curatively
treated carcinoma in situ or basal cell carcinoma of the skin

- No known sensitivity to any of the study medication components (i.e., polyethylene
glycol [PEG 300] and 2-hydroxypropyl β-cyclodextrin)

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- At least 3 months since prior radiation therapy

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- At least 2 weeks since prior Federal Drug Administration (FDA)-approved noncytotoxic
therapy (e.g., celecoxib or thalidomide)

- At least 3 weeks since prior investigational noncytotoxic agents

- At least 10 days since prior anticonvulsant drugs that induce hepatic metabolic
enzymes, including any of the following:

- Phenytoin

- Carbamazepine

- Phenobarbital

- Primidone

- Oxcarbazepine

- Ethosuximide

- No other concurrent therapy for this tumor, including systemic chemotherapy or
radiation therapy

- Concurrent steroids allowed